Liposuction evolved from work in the late 1960s from surgeons in Europe using primitive curettage techniques which were largely ignored, as they achieved irregular results with significant morbidity and bleeding. Modern liposuction first burst on the scene in a presentation by the French surgeon, Dr Yves-Gerard Illouz, in 1982. The “Illouz Method” featured a technique of suction-assisted lipolysis after tumesing or infusing fluid into tissues using blunt cannulas and high-vacuum suction and demonstrated both reproducible good results and low morbidity. During the 1980s, many United States surgeons experimented with liposuction, developing variations, and achieving mixed results. Most commonly, liposuction is performed on the abdomen and thighs in women, and the abdomen and flanks in men. According to the most recent statistics by the American Society for Aesthetic Plastic Surgery, liposuction, including conventional suction-assisted lipectomy (SAL), ultrasound-assisted liposuction (UAL), and laser-assisted liposuction (LAL), is the most common aesthetic procedure performed by plastic surgeons in the United States. However, these procedures are often associated with secondary complications such as contour deformities, irregular lumpy appearance, and excess skin, leading to patient dissatisfaction.
Traditional liposuction relies on two techniques. The first technique employs a sharp, relatively large diameter (3 mm-5 mm) cannula that is manually manipulated to mechanically break fat down and while applying suction to remove the separated fat. A variation of this vacuum assisted technique is a mechanically powered cannula that reduces the surgeon's fatigue during large surface area liposuction procedures.
The second technique utilizes ultrasonic waves via a vibrating cannula, this technique is mechanical in its nature and significantly reduces the surgeon's fatigue factor. This technique induces the same or worse mechanical trauma to the tissues. Both techniques require significant amounts of fluid, known as a “tumescent solution,” to be injected into the body to emulsify the fat, facilitating the removal of large volumes of fat while reducing blood loss and delivering a local anesthetic (lidocaine) to provide post-operative pain relief. While generally safe, lidocaine can be toxic, leading to serious complications, and even death.
A problem with the probes used in existing liposuction procedures is the generation of significant amounts of heat at the distal tip of the probe, which can exceed the temperature required for melting the fatty tissue. This excess heat can result in burning of tissue, damaging muscles or blood vessels, and even penetrating membranes such as the skin or the peritoneum that covers most of the intra-abdominal organs.
Alternative methods have been disclosed which exploit laser energy to remove unwanted fat, known as laser-assisted liposuction (LAL). Current FDA-approved technologies for LAL rely predominantly on wavelengths around or beyond 1000 nm, where water absorbs and emits heat. As a result, these methods require the insertion of laser probes into the subcutaneous tissue to liquefy small volumes of fat. Because of the point source nature of the heating device, results are not uniform, and surrounding subcutaneous tissue, such as muscle and fibrous connective tissues, may also be heated. Further, because such systems rely on endogenous chromophores such as water or hemoglobin, their concentration is fixed.
U.S. Pat. Nos. 6,605,080 and 7,060,061, both issued to Altshuler, et al. represent an alternative approach in which laser energy is externally applied to the skin to heat and melt fat tissue in epidermis and subcutaneous layers below. These patents disclose the use of near- to mid-infrared radiation wavelengths that are preferentially absorbed by lipid cells to heat-liquefy fat cells, after which the lipid pool may be removed from the subcutaneous area by aspiration. The need to fine-tune the laser wavelength for preferential absorption by the lipid cells, as well as the considerable heat generation that results from the techniques, e.g., up to 70° C., at or in the fat tissue, require use of a cooling mechanism to prevent skin damage or permanent scarring. These methods present other limitations and potential adverse thermal effects on tissue above the lipid-rich tissue under treatment, including blistering, peeling, and depigmentation.
U.S. Pat. No. 8,357,146 of Hennings discloses a LAL device and method in which wavelengths of pulsed laser radiation that are preferentially absorbed by lipid cells are applied directly to the tissue by inserting a fiber optic probe into the target area. As in Altschuler's method, the direct absorption of the laser energy heats the fat, however, this heating is augmented by a coating on the optical fiber that absorbs the laser energy and acts as a hot tip, or “char”, to ablate and disrupt tissue. This high temperature char creates a risk of accidental damage to surrounding tissue.
U.S. Pat. No. 8,430,919 of Bornstein discloses a lipolysis method in which the skin over the target site is optically irradiated with two different wavelengths of light, one in the near infrared (NIR) region, the other in the infrared range, to modulate biochemical processes of adipocytes in the target site. In order to achieve the desired degree of fat removal, the duration of the treatment must be relatively long, from one to two hours, during which the patient must remain virtually motionless. Unless a sedative or general anesthesia has been administered to calm the patient, physical and psychological discomfort can ensue.
NIR (700-950 nm) is preferable to other types of light for therapeutic use in biological systems because NIR light can pass through blood and tissue to depths of several inches. However, very few organic chromophores absorb in this region, and even fewer are capable of converting the absorbed energy into a chemical or thermal response that can be used to trigger drug release. A few years ago, gold nanostructures (shells, particles, rods, and cages) emerged as useful agents for photothermal therapy after they were shown to have strong absorption in the NIR region (four to five times higher than conventional photo-absorbing dyes) as well as tunable optical resonances. The strong absorption enables effective laser therapy at relatively low laser energies, rendering such therapy methods minimally invasive.
Laser photothermal therapy of cancer with the use of gold nanoparticles immunotargeted to molecular markers has been reported as being effective to selectively kill cancer cells at lower laser powers than those needed to kill healthy cells. (X. Huang, et al., “Determination of the Minimum Temperature Required for Selective Photothermal Destruction of Cancer Cells with the Use of Immunotargeted Gold Nanoparticles”, Photochemistry and Photobiology, 2006, 82:412-417.) Gold nanoparticles absorb light efficiently in the visible region due to coherent oscillations of metal conduction band electrons in strong resonance with visible frequencies of light, a phenomenon known as “surface plasmon resonance” or “SPR”. Photoexcitation of metal nanostructures results in the formation of a heated electron gas that cools rapidly, e.g., within 1 ps, by exchanging energy with the nanoparticle lattice. The nanoparticle lattice, in turn, rapidly exchanges energy with the surrounding medium on the timescale of 100 ps, causing localized heating. This rapid energy conversion and dissipation can be achieved by using light radiation with a frequency that strongly overlaps the nanoparticle absorption band.
U.S. Patent Publication 2012/0059307 of Harris et al. discloses a method of selective thermomodulation in tissue that applies nanoparticles to a target tissue region that is then irradiated with laser light to induce thermal damage to destroy or remove the tissue by ablation. Ablation involves the cutting or removal of tissue by fracture of chemical bonds through phase transitions consisting of vaporization, molecular fragmentation, and/or void formation, i.e., a violent, destructive process. (See, e.g., A. Vogel and V. Venugopalan, “Mechanisms of Pulsed Laser Ablation of Biological Tissues”, Chem. Rev. 2003, 103, 577-644.) Harris' et al.'s target tissue includes hair follicles, sebaceous glands, and unwanted or diseased vasculature, where destruction (necrosis or apoptosis) of the target tissue is the goal. However, for applications where actual destruction of the tissue is not desirable, this approach is not appropriate.
The conditions for irradiation as well as the nanoparticle characteristics are critical for obtaining the necessary control for providing effective treatment while avoiding tissue damage. Nanorods exhibit cylindrical symmetry, and simple changes in particle symmetry can significantly alter SPR characteristics. The NIR absorption maximum of metal nanostructures can be modulated by changing their size, shape and aggregation. GNRs have two plasmon absorption peaks, exhibiting transverse and longitudinal surface plasmon resonances that correspond to electron oscillations perpendicular and parallel to the rod length direction, respectively. The longitudinal surface plasmon wavelengths are tunable from the visible to infrared regions. The effectiveness of GNRs as photothermal therapeutic agents is strongly dependent on their scattering and absorption cross-sections—large absorption cross sections with small scattering losses allow for photothermal therapy with a minimal laser dosage. In addition, the longitudinal surface plasmon wavelengths of GNRs are preferably within the spectral range of 650-900 nm. Light irradiation in this region can penetrate more deeply into tissues and cause less photodamage than UV-visible irradiation. Therefore, the ability to tailor both scattering and absorption of GNRs with different longitudinal surface plasmon wavelengths is important for therapeutic applications.